The following description is provided to assist the understanding of the reader. None of the information provided or references cited is admitted to be prior art to the present invention.
Red blood cell (RBC) aggregation has been widely studied and its importance is well established in the rheology of microcirculation (Aleksander S et al. 2005; E. Vicaut et al. 1994; J. J. Durussel et al. 1998). Three significant factors responsible for microcirculatory blood flow disorders are the increased RBC aggregation, increased plasma viscosity and lowered erythrocyte deformability (S Chien et al. 1987; G. Cicco et al. 1999; V. Nagaprasad et al. 1998). Under physiological conditions, the RBC in static or slowly moving blood can adhere to each other like piles of coins to form reversible cell-to-cell contact leading to formation of aggregates.
RBC aggregation increases blood viscosity and thus affects the passage of the cells through microvessels, especially in venules (Mark J et al. 2000; George Mchedlishvili et al. 2002). In pathological conditions, RBCs can form irreversible or less reversible aggregates, which are capable of plugging arterioles and venules. Abnormal RBC aggregation has been found to be associated with several diseases and conditions, including diabetes, malaria, heart failure, ischemic heart diseases, stroke, brain hypoperfusion, ischemic limbs, hypertension, hematological disorders, anesthesia and many others (John A et al. 1979; Amiram Eldor et al. 2002; Patricia foresto et al. 2000).
The RBC diameter is larger than the average diameter of capillary, and therefore RBCs must deform to pass through capillaries one at a time, in boxcar fashion. However, RBC aggregates are not able to pass through capillaries. Hence, extensive RBC aggregation would increase blood viscosity and reduce the effective blood perfusion of important organs and the whole body.
In normal blood, RBC aggregation is a reversible process in the presence of adequate shear forces. However, pathological RBC aggregation forms rapidly and extensively. Currently available therapeutic approaches or drugs can only offer relief of symptoms or slow down the progressive worsening of the condition. Effective separation of the aggregated RBC and prevention of RBC from further aggregation would significantly improve microcirculation that would further contribute to the effective prevention or treatment of many severe diseases, such as heart attack, stroke, ischemic heart diseases, heart failure, hypertension, ischemic limbs, brain hypoperfusion, and wound healing, especially in aged populations.